Epidemiological aspects in phenylketonuria patients from a region in northwestern Romania

Q4 Medicine
A. Iuhas, Claudia Jurca, M. Bembea
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The aim of this study is the determination of the impact of non-genetic factors over the clinical phenotype of PKU patients in a region of north-west Romania. Material and method. The study group is formed from 44 patients diagnosed with phenylketonuria in the 1981 – 2021 period, found in the database of Bihor Regional Center for Medical Genetics, Emergency Clinical County Hospital, Oradea, Romania. The collected data was referring to the age, sex and domicile of the patients, the age of the diagnosis and the beginning of the treatment, also the metabolic control over the years, the metabolic phenotype of the patients and its impact on the clinical phenotype (IQ, the presence or absence of intellectual disability or the existence of a specific clinical phenotype). Results. The majority of patients (66%) were diagnosticated with phenylketonuria in the first 4 months of life, although there were cases with a late diagnosis, 20.5% of the patients were diagnosticated after the age of 1 year. Based on the pre-treatment plasmatic levels of phenylalanine, the majority of cases (72.7%) had a severe metabolic phenotype (classic PKU - cPKU), 20.5% of cases had a milder form of PKU (mPKU) and 6.8% of patients were found with a mild hyperphenylalaninemia (HPA). In the case of 23 patients, an optimal metabolic control was not obtained. The specific phenotype (blonde hair, light skin, blue eyes) was found in 22.7% of cases, 77.3% not having these features. At 68.2% of cases intellectual disability was found, with different levels of severity: 5 patients (11.5%) had liminal intellect, 9 patients (20.5%) had mild mental retardation, 6 patients (13.6%) had moderate mental retardation, 9 cases (20.5%) were with severe mental retardation and 1 patient (2.3%) had profound mental retardation; 31.8% of cases had normal intellect. The prevalence in Bihor county is 1:7,843 newborns. Discussions. A partial or, in rare cases, total lack of dietetic treatment was observed in all patients over 20 years old (current age). The delay in treatment initiation or an insufficient treatment, with a suboptimal metabolic control, will affect patient’s intellect, regardless of metabolic phenotype. If in 20 years old patients, or older, the main reason for mental retardation is the lack of dietetic treatment availability in the first years of life, for the younger patients the reason for mental retardation is usually a lack of compliance with the treatment. The majority of metabolic phenotypes is cPKU, in concordance with the literature data; the mild phenotype (HPA) was observed in a small percentage of patients, smaller than the data reported in the literature. In the first two studied decades the mild phenotypes were seldom observed. In the absence of screening tests or suggestive clinical manifestation it can be assumed that HPA patients remained undiagnosed, which would explain the small HPA percentage in the study group. A significant improvement in metabolic control in younger patients compared with older ones was observed, which denotes a better access to specific alimentation on one side, and o the other side, a better understanding of the disease from the patients and their families. Also, this study confirms a known fact that the diet in PKU is of great importance in the disease evolution. In this study there were included patients with severe metabolic phenotype with good metabolic control which reached adulthood without intellectual deficits, with higher education, social integrated and also patients with mild metabolic phenotype but with a poor metabolic control which developed intellectual deficiency. Conclusions. The PKU prevalence in Bihor county is higher than the estimated national value. The late diagnosis and treatment or the poor metabolic control led to intellectual disability, regardless of the metabolic phenotype. PKU screening and the better access to treatment allows younger generations of patients to enjoy a superior quality of life than the patients from the first two studied decades.","PeriodicalId":33512,"journal":{"name":"Revista Romana de Pediatrie","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Revista Romana de Pediatrie","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.37897/rjp.2022.2.2","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 1

Abstract

Introduction. Phenylketonuria (PKU), a genetic disease with autosomal dominant transmission, is the most frequent inborn error in aminoacidic metabolism. The variations in phenylalanine-hydroxylase (PAH) gene lead to a lowered enzymatic activity causing hyperphenylalaninemia. PKU has a mean European prevalence of 1:10,000 newborns, with a large variation in different ethnicities and geographic regions. The large genetic variability (over 1200 genetic variants known) as well as other factors determines a wide spectrum of metabolic phenotypes. Untreated, PKU leads to irreversible intellectual disability, low stature, hypopigmentation, motor deficits, seizures, but the early diagnosis and treatment enables almost normal somatic and mental development. Aim. The aim of this study is the determination of the impact of non-genetic factors over the clinical phenotype of PKU patients in a region of north-west Romania. Material and method. The study group is formed from 44 patients diagnosed with phenylketonuria in the 1981 – 2021 period, found in the database of Bihor Regional Center for Medical Genetics, Emergency Clinical County Hospital, Oradea, Romania. The collected data was referring to the age, sex and domicile of the patients, the age of the diagnosis and the beginning of the treatment, also the metabolic control over the years, the metabolic phenotype of the patients and its impact on the clinical phenotype (IQ, the presence or absence of intellectual disability or the existence of a specific clinical phenotype). Results. The majority of patients (66%) were diagnosticated with phenylketonuria in the first 4 months of life, although there were cases with a late diagnosis, 20.5% of the patients were diagnosticated after the age of 1 year. Based on the pre-treatment plasmatic levels of phenylalanine, the majority of cases (72.7%) had a severe metabolic phenotype (classic PKU - cPKU), 20.5% of cases had a milder form of PKU (mPKU) and 6.8% of patients were found with a mild hyperphenylalaninemia (HPA). In the case of 23 patients, an optimal metabolic control was not obtained. The specific phenotype (blonde hair, light skin, blue eyes) was found in 22.7% of cases, 77.3% not having these features. At 68.2% of cases intellectual disability was found, with different levels of severity: 5 patients (11.5%) had liminal intellect, 9 patients (20.5%) had mild mental retardation, 6 patients (13.6%) had moderate mental retardation, 9 cases (20.5%) were with severe mental retardation and 1 patient (2.3%) had profound mental retardation; 31.8% of cases had normal intellect. The prevalence in Bihor county is 1:7,843 newborns. Discussions. A partial or, in rare cases, total lack of dietetic treatment was observed in all patients over 20 years old (current age). The delay in treatment initiation or an insufficient treatment, with a suboptimal metabolic control, will affect patient’s intellect, regardless of metabolic phenotype. If in 20 years old patients, or older, the main reason for mental retardation is the lack of dietetic treatment availability in the first years of life, for the younger patients the reason for mental retardation is usually a lack of compliance with the treatment. The majority of metabolic phenotypes is cPKU, in concordance with the literature data; the mild phenotype (HPA) was observed in a small percentage of patients, smaller than the data reported in the literature. In the first two studied decades the mild phenotypes were seldom observed. In the absence of screening tests or suggestive clinical manifestation it can be assumed that HPA patients remained undiagnosed, which would explain the small HPA percentage in the study group. A significant improvement in metabolic control in younger patients compared with older ones was observed, which denotes a better access to specific alimentation on one side, and o the other side, a better understanding of the disease from the patients and their families. Also, this study confirms a known fact that the diet in PKU is of great importance in the disease evolution. In this study there were included patients with severe metabolic phenotype with good metabolic control which reached adulthood without intellectual deficits, with higher education, social integrated and also patients with mild metabolic phenotype but with a poor metabolic control which developed intellectual deficiency. Conclusions. The PKU prevalence in Bihor county is higher than the estimated national value. The late diagnosis and treatment or the poor metabolic control led to intellectual disability, regardless of the metabolic phenotype. PKU screening and the better access to treatment allows younger generations of patients to enjoy a superior quality of life than the patients from the first two studied decades.
罗马尼亚西北部一地区苯丙酮尿症患者的流行病学特征
介绍苯丙酮尿症(PKU)是一种常染色体显性遗传疾病,是氨基酸代谢中最常见的先天性错误。苯丙氨酸羟化酶(PAH)基因的变异导致酶活性降低,导致高苯丙氨酸血症。PKU在欧洲的平均发病率为1:10000新生儿,不同种族和地理区域的发病率差异很大。巨大的遗传变异性(已知1200多种遗传变异)以及其他因素决定了广泛的代谢表型。如果不治疗,PKU会导致不可逆转的智力残疾、身材矮小、色素沉着不足、运动缺陷、癫痫发作,但早期诊断和治疗可以使身体和精神发育几乎正常。目标本研究的目的是确定非遗传因素对罗马尼亚西北部地区PKU患者临床表型的影响。材料和方法。该研究小组由罗马尼亚奥拉迪亚县急诊临床县医院比霍尔地区医学遗传学中心的数据库中发现的1981年至2021年期间诊断为苯丙酮尿症的44名患者组成。收集的数据涉及患者的年龄、性别和住所、诊断年龄和治疗开始时间、多年来的代谢控制、患者的代谢表型及其对临床表型的影响(IQ、是否存在智力残疾或是否存在特定临床表型)。后果大多数患者(66%)在生命的前4个月被诊断为苯丙酮尿症,尽管也有诊断较晚的病例,但20.5%的患者在1岁后被诊断。根据治疗前血浆苯丙氨酸水平,大多数病例(72.7%)具有严重的代谢表型(典型的PKU-cPKU),20.5%的病例具有较轻形式的PKU(mPKU),6.8%的患者患有轻度高苯丙氨酸血症(HPA)。在23名患者的情况下,没有获得最佳的代谢控制。在22.7%的病例中发现了特定的表型(金发、浅色皮肤、蓝色眼睛),77.3%的病例没有这些特征。68.2%的病例发现智力残疾,其严重程度不同:5例(11.5%)为智力极限,9例(20.5%)为轻度智力迟钝,6例(13.6%)为中度智力迟钝,9例为重度智力迟钝,1例(2.3%)为深度智力迟钝;智力正常者占31.8%。比霍尔县的新生儿患病率为1:7843。讨论。在所有20岁以上(当前年龄)的患者中观察到部分或在极少数情况下完全缺乏饮食治疗。无论代谢表型如何,治疗开始延迟或治疗不足,代谢控制不理想,都会影响患者的智力。如果在20岁或以上的患者中,精神发育迟缓的主要原因是在生命的最初几年缺乏饮食治疗,那么对于年轻患者来说,精神发育迟滞的原因通常是缺乏对治疗的依从性。大多数代谢表型是cPKU,与文献数据一致;轻度表型(HPA)在一小部分患者中观察到,比文献中报道的数据要小。在研究的前二十年中,很少观察到温和的表型。在没有筛查测试或提示性临床表现的情况下,可以假设HPA患者仍未确诊,这可以解释研究组中HPA比例较小的原因。与老年患者相比,年轻患者的代谢控制有了显著改善,这意味着一方面可以更好地获得特定的营养,另一方面,患者及其家人对疾病有了更好的了解。此外,这项研究证实了一个已知的事实,即北大的饮食在疾病进化中具有重要意义。在这项研究中,包括具有严重代谢表型且代谢控制良好的患者,这些患者成年后没有智力缺陷,受过高等教育,社会融合,也包括具有轻度代谢表型但代谢控制不良并发展为智力缺陷的患者。结论。比霍尔县的PKU患病率高于全国估计值。无论代谢表型如何,诊断和治疗较晚或代谢控制不佳都会导致智力残疾。PKU筛查和更好的治疗机会使年轻一代的患者比前二十年的患者享有更高的生活质量。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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